The development of Lewisite vapour induced lesions in the domestic, white pig.
(25/2324)
Studies performed in the past in our laboratory have detailed the development of sulphur mustard lesions in the domestic, white pig using small glass chambers to achieve saturated vapour exposure under occluded conditions. We have now used this experimental model to produce cutaneous lesions for detailed histopathological studies following challenge with lewisite. Histological examination of resulting lesions have revealed that although the overall pattern of lesion development is similar to that seen following mustard challenge, the time-course of cellular events is very much compressed. The epidermis showed focal basal cell vacuolation with associated acute inflammation as early as one hour postexposure. Coagulative necrosis of the epidermis and papillary dermis was complete by 24 hours and followed the appearance of multiple coalescent blisters between six and 12 hours post-exposure. At 48 hours, the lesions were full thickness burns with necrosis extending into the deep subcutaneous connective and adipose tissues. The study of lesions beyond 24 hours revealed early epithelial regeneration at the wound edge. The overall spontaneous healing rate of these biologically severe lesions was significantly faster than comparable sulphur mustard injuries and probably reflected a lack of alkylation of DNA and RNA. (+info)
The head domain of plakophilin-1 binds to desmoplakin and enhances its recruitment to desmosomes. Implications for cutaneous disease.
(26/2324)
The contribution of desmosomes to epidermal integrity is evident in the inherited blistering disorder associated with the absence of a functional gene for plakophilin-1. To define the function of plakophilin-1 in desmosome assembly, interactions among the desmosomal cadherins, desmoplakin, and the armadillo family members plakoglobin and plakophilin-1 were examined. In transient expression assays, plakophilin-1 formed complexes with a desmoplakin amino-terminal domain and enhanced its recruitment to cell-cell borders; this recruitment was not dependent on the equimolar expression of desmosomal cadherins. In contrast to desmoplakin-plakoglobin interactions, the interaction between desmoplakin and plakophilin-1 was not mediated by the armadillo repeat domain of plakophilin-1 but by the non-armadillo head domain, as assessed by yeast two-hybrid and recruitment assays. We propose a model whereby plakoglobin serves as a linker between the cadherins and desmoplakin, whereas plakophilin-1 enhances lateral interactions between desmoplakin molecules. This model suggests that epidermal lesions in patients lacking plakophilin-1 are a consequence of the loss of integrity resulting from a decrease in binding sites for desmoplakin and intermediate filaments at desmosomes. (+info)
Epidermal diseases in bottlenose dolphins: impacts of natural and anthropogenic factors.
(27/2324)
Experimental studies have highlighted the potential influence of contaminants on marine mammal immune function and anthropogenic contaminants are commonly believed to influence the development of diseases observed in the wild. However, estimates of the impact of contaminants on wild populations are constrained by uncertainty over natural variation in disease patterns under different environmental conditions. We used photographic techniques to compare levels of epidermal disease in ten coastal populations of bottlenose dolphins (Tursiops truncatus) exposed to a wide range of natural and anthropogenic conditions. Epidermal lesions were common in all populations (affecting > 60% of individuals), but both the prevalence and severity of 15 lesion categories varied between populations. No relationships were found between epidermal disease and contaminant levels across the four populations for which toxicological data were available. In contrast, there were highly significant linear relationships with oceanographic variables. In particular, populations from areas of low water temperature and low salinity exhibited higher lesion prevalence and severity. Such conditions may impact on epidermal integrity or produce more general physiological stress, potentially making animals more vulnerable to natural infections or anthropogenic factors. These results show that variations in natural environmental factors must be accounted for when investigating the importance of anthropogenic impacts on disease in wild marine mammals. (+info)
Profilaggrin requires both linker and filaggrin peptide sequences to form granules: implications for profilaggrin processing in vivo.
(28/2324)
Filaggrin is an intermediate filament associated protein that aids the packing of keratin filaments during terminal differentiation of keratinocytes. Premature aggregation of keratin filaments is prevented by filaggrin expression as the inactive precursor, profilaggrin, which is localized in keratohyalin granules in vivo. Profilaggrin is phosphorylated and contains multiple filaggrin repeats separated by a hydrophobic linker peptide. We have previously shown that filaggrin constructs containing the linker, when transiently transfected into epithelial cells, lead to expression of a protein that resembles keratohyalin (Dale et al. J Invest Dermatol 108:179-187 1997). To characterize further the region(s) of the linker and/or filaggrin that are necessary for granule formation, we generated several mutant constructs from Flag-FG-1, and generated fusions of filaggrin with green fluorescent protein. We also subjected profilaggrin to protein phosphatase 2A treatment and measured its subsequent solubility. We found that granular morphology is not dependent on the linker or conserved phosphorylation sites, nor is solubility affected by protein phosphatase 2A treatment. Granule morphology was abrogated only in a truncated construct, which still contains the linker. A construct consisting of 16 amino acids of filaggrin fused to green fluorescent protein led to rounded and bizarrely shaped transfected cells with compact keratin filaments, suggesting that very little filaggrin sequence is required for keratin filament interaction. Radiolabeled filaggrin-green fluorescent protein constructs specifically bound keratin in overlay assays confirming that the observed cytoskeletal collapse is due to filaggrin-keratin interaction. Our findings indicate that profilaggrin must be extensively processed before it loses both its granule forming ability as well as its insolubility, suggesting that granule formation in vivo correlates with insolubility in vitro. Further, filaggrin retains its ability to bind keratin as it is degraded to smaller peptides. (+info)
Occupational dermatoses in farmers - a proposal for diagnostic procedure.
(29/2324)
The article presents a proposal for diagnostic procedures in cases of suspected occupational dermatosis in farmers. The process of certifying a disease as occupational is difficult because of lack of the monitoring of occupational risks in private farms; moreover, there is no compulsory medical assessment before one starts work as a farmer. Many patients meet an occupational health professional for the first time when the disease is already advanced and legal action towards obtaining an occupational rent has already been issued. In these circumstances, confirming or rejecting the possible occupational etiology of a given dermatosis is very difficult. This article presents a diagnostic procedure which has been devised by the author and used with some success for two years at the Institute of Agricultural Medicine, Lublin, Poland. (+info)
The burden of mucocutaneous conditions and the association with HIV-1 infection in a rural community in Uganda.
(30/2324)
OBJECTIVE: To determine the prevalence of mucocutaneous conditions and their association with HIV-1 infection in a rural community in Uganda. METHODS: In a prospective cohort study, participants were recruited from a large population study and invited to attend a clinic every 3 months for a detailed medical interview and a thorough physical examination. All findings including mucocutaneous findings were coded onto a standard questionnaire. RESULTS: By the end of 1996, 436 participants had provided 1450 person years of observation (pyo); 646 pyo in HIV-positives and 804 pyo in HIV-negatives. Overall, 70% of participants had a skin condition during follow-up, and although skin conditions were significantly more common in HIV-positive subjects, the background level in HIV-negative subjects was high (77.3% and 63.6%, respectively). Herpes zoster, thin/sparse hair, maculo-papular rash and prurigo were significantly more common in the HIV-positives. Kaposi sarcoma, palmar/plantar rash and herpes zoster had positive predictive values for HIV infection of over 80%. Oral conditions were found in over 40% of participants and were significantly more common in HIV-positive subjects. Oral candidiasis and Kaposi sarcoma were significantly more frequent among HIV-positives. CONCLUSION: HIV infection increases the already high burden of mucocutaneous diseases in this rural population. We identified some conditions that are more common in HIV and others that can be used as indicators of HIV infection. (+info)
Calcinosis cutis and intestinal pseudoobstruction in a patient with adult onset Still's disease associated with recurrent relapses of disordered coagulopathy.
(31/2324)
Adult onset Still's disease (AOSD) is a systemic inflammatory disorder of unknown origin, characterized by a typical spiking fever, evanescent salmon-colored rash, polyarthralgia, and myalgia. Calcinosis cutis and gastrointestinal involvement have rarely been noted in AOSD. We herein describe a 54-year-old woman who demonstrated repeated disseminated intravascular coagulation (DIC), and adult respiratory distress syndrome (ARDS), associated with AOSD. The patient also revealed a remarkable degree of digital calcinosis cutis and intestinal pseudoobstruction. A connective tissue disease, such as systemic sclerosis, might have been the underlying factor in the latter two symptoms. (+info)
Skin bruising, adrenal function and markers of bone metabolism in asthmatics using inhaled beclomethasone and fluticasone.
(32/2324)
Fluticasone propionate (FP) is generally considered to have twice the efficacy of beclomethasone dipropionate (BDP) on a weight-to-weight basis for the control of asthma, and may have lesser effects on adrenal function. However, the effects of FP and BDP on skin integrity and bone metabolism markers require further examination. Sixty-nine asthmatic subjects were enrolled in a double-blind crossover study in which, after a baseline period, they received BDP or FP (at half the dose of BDP) for two 4-month periods each. A questionnaire on skin bruising, a skin examination, tests of adrenal function and of markers of bone metabolism were performed after 2 months of each period. The number of asthma exacerbations was not significantly different for the two treatment periods (eight for BDP and nine for FP), nor were various indices of asthma control. Whereas the frequency of bruising reported by the questionnaire was not different, there were more bruises on examination for BDP (1.6+/-2.5) than for FP (1.2+/-2.3) (p=0.04). Although baseline serum cortisol was not significantly different for the two drugs, the increase in cortisol after cortrosyn was lower for BDP (357+/-158 micromol x dL(-1)) than for FP (422+/-144 micromol x dL(-1)) (p<0.01). Serum osteocalcin levels were significantly lower in subject on BDP (2.8+/-1.7 microg x mL(-1)) than on FP (3.5+/-1.9 ng x mL(-1)) (p=0.003). Other markers of bone metabolism were not significantly altered. The three major side-effects were loosely, but significantly correlated with the periods on BDP and FP. However, skin bruises, increase in cortisol after Cortrosyn and osteocalcin were not significantly correlated for the period on either BDP or FP. In conclusion, whereas fluticasone propionate used at half the dose of beclomethasone dipropionate has a comparable effect on the control of asthma, fluticasone propionate demonstrated fewer side-effects in terms of skin bruising, adrenal suppression and bone metabolism. (+info)